The Manhattan HIV Brain Bank (MHBB), member of the National NeuroAIDS Tissue Consortium (NNTC), has been a resource for the neuroAIDS research community since 1998. It performs neurologic, neuropsychological, psychiatric, general medical, and autopsy pathology assessments on a cohort of predominantly HIV-infected individuals, who agree to be organ donors upon demise, for the purposes of neuroAIDS and AIDS research. As a result of MHBB's observational longitudinal study, its tissue and fluids resources are densely annotated, and support a wide range of investigations into HIV-associated central (CNS) and peripheral nervous system (PNS) disorders. In the next cycle, MHBB will participate with other members of the NNTC to create a cohort optimized for the study of CNS reservoirs, aging, and pathogenesis of HIV-associated cognitive disorders persisting in the face of antiretroviral therapy. Specifically, MHBB will increase its representatin of older individuals, and those with stably suppressed plasma viral loads following variable CD4 nadirs. With this transition, MHBB will maintain important cohort characteristics reflective of the NYC epidemic, including prominent representation of minorities, women, and socio-culturally and medically complex individuals. MHBB will regularly upload clinical and pathologic information into a central consortium database, participate in all the protocol-defining and qualit assurance programs of the NNTC, and distribute its information, tissues, and fluids to investigators through central processes led by the NNTC data coordination center. MHBB will continue to analyze the behavioral and neurologic phenotypes of its cohort, to better understand how neuroAIDS disorders manifest in aging, demographically diverse individuals living through changes in therapeutic eras. Through observational studies, MHBB will better serve neuroAIDS researchers, as careful delineation of phenotype will assure better assignment of resources to research designs. Furthermore, observational study of HIV-associated CNS and PNS disease will allow MHBB to better understand neurobiologically relevant methods for subject characterization, and how to continue modifications of the cohort as the HIV epidemic continues to evolve.